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2025 demonstrates that chronic GCGR agonism downregulates hepatocyte PDE4B/4D phosphodiesterases, producing sustained cAMP-PKA signaling that preserves resting energy expenditure against the adaptive decline of weight loss

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We observed an increased resting energy expenditure in mouse models of obesity/metabolic syndrome that was associated with increased fatty acid oxidation leading to improvements in glucose tolerance and decreasing adiposity

2009;296:C124857